Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy

Ana Morales, Thomas Painter, Ran Li, Jill D. Siegfried, Duanxiang Li, Nadine Norton, Ray E. Hershberger

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

BACKGROUND-: The term peripartum cardiomyopathy (PPCM) describes dilated cardiomyopathy (DCM) without known cause that occurs during the last month of pregnancy to 5 months postpartum. A related term, pregnancy-associated cardiomyopathy (PACM), refers to DCM onset earlier in pregnancy. Multiple studies have focused on inflammatory, immunologic, and environmental causes. An alternative hypothesis is that PPCM and PACM result, in part, from a genetic cause. In this study, we sought to test the hypothesis that rare DCM-associated mutations underlie a proportion of PACM or PPCM cases. METHODS AND RESULTS-: A systematic search of our DCM database designed for family-based genetic studies was undertaken for cases associated with pregnancy and the postpartum period; in the identified cases, clinical and molecular genetic data, including exonic and near intron/exon boundaries of DCM genes, were analyzed. Of 4110 women from 520 pedigrees in the Familial Dilated Cardiomyopathy Research Project database, we identified 45 cases of PPCM/PACM. Evidence of familial clustering with DCM was present in 23 unrelated cases. Of the 45 cases, 19 had been resequenced for known DCM genes, and 6 carried mutations. Five had PPCM, of which 3 were familial with mutations found in MYH7, SCN5A, and PSEN2, and 2 were sporadic with mutations in MYH6 and TNNT2. One case had PACM and carried a mutation in MYBPC3. CONCLUSIONS-: These findings suggest that a proportion of PPCM/PACM cases results from a genetic cause.

Original languageEnglish (US)
Pages (from-to)2176-2182
Number of pages7
JournalCirculation
Volume121
Issue number20
DOIs
StatePublished - May 25 2010
Externally publishedYes

Fingerprint

Peripartum Period
Cardiomyopathies
Dilated Cardiomyopathy
Pregnancy
Mutation
Postpartum Period
Databases
Pedigree
Introns
Genes
Cluster Analysis
Molecular Biology
Exons

Keywords

  • Cardiomyopathy
  • Genetics
  • Pregnancy complications

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Morales, A., Painter, T., Li, R., Siegfried, J. D., Li, D., Norton, N., & Hershberger, R. E. (2010). Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy. Circulation, 121(20), 2176-2182. https://doi.org/10.1161/CIRCULATIONAHA.109.931220

Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy. / Morales, Ana; Painter, Thomas; Li, Ran; Siegfried, Jill D.; Li, Duanxiang; Norton, Nadine; Hershberger, Ray E.

In: Circulation, Vol. 121, No. 20, 25.05.2010, p. 2176-2182.

Research output: Contribution to journalArticle

Morales, A, Painter, T, Li, R, Siegfried, JD, Li, D, Norton, N & Hershberger, RE 2010, 'Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy', Circulation, vol. 121, no. 20, pp. 2176-2182. https://doi.org/10.1161/CIRCULATIONAHA.109.931220
Morales, Ana ; Painter, Thomas ; Li, Ran ; Siegfried, Jill D. ; Li, Duanxiang ; Norton, Nadine ; Hershberger, Ray E. / Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy. In: Circulation. 2010 ; Vol. 121, No. 20. pp. 2176-2182.
@article{242c92234b08409caf0869d1ad80dbaf,
title = "Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy",
abstract = "BACKGROUND-: The term peripartum cardiomyopathy (PPCM) describes dilated cardiomyopathy (DCM) without known cause that occurs during the last month of pregnancy to 5 months postpartum. A related term, pregnancy-associated cardiomyopathy (PACM), refers to DCM onset earlier in pregnancy. Multiple studies have focused on inflammatory, immunologic, and environmental causes. An alternative hypothesis is that PPCM and PACM result, in part, from a genetic cause. In this study, we sought to test the hypothesis that rare DCM-associated mutations underlie a proportion of PACM or PPCM cases. METHODS AND RESULTS-: A systematic search of our DCM database designed for family-based genetic studies was undertaken for cases associated with pregnancy and the postpartum period; in the identified cases, clinical and molecular genetic data, including exonic and near intron/exon boundaries of DCM genes, were analyzed. Of 4110 women from 520 pedigrees in the Familial Dilated Cardiomyopathy Research Project database, we identified 45 cases of PPCM/PACM. Evidence of familial clustering with DCM was present in 23 unrelated cases. Of the 45 cases, 19 had been resequenced for known DCM genes, and 6 carried mutations. Five had PPCM, of which 3 were familial with mutations found in MYH7, SCN5A, and PSEN2, and 2 were sporadic with mutations in MYH6 and TNNT2. One case had PACM and carried a mutation in MYBPC3. CONCLUSIONS-: These findings suggest that a proportion of PPCM/PACM cases results from a genetic cause.",
keywords = "Cardiomyopathy, Genetics, Pregnancy complications",
author = "Ana Morales and Thomas Painter and Ran Li and Siegfried, {Jill D.} and Duanxiang Li and Nadine Norton and Hershberger, {Ray E.}",
year = "2010",
month = "5",
day = "25",
doi = "10.1161/CIRCULATIONAHA.109.931220",
language = "English (US)",
volume = "121",
pages = "2176--2182",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "20",

}

TY - JOUR

T1 - Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy

AU - Morales, Ana

AU - Painter, Thomas

AU - Li, Ran

AU - Siegfried, Jill D.

AU - Li, Duanxiang

AU - Norton, Nadine

AU - Hershberger, Ray E.

PY - 2010/5/25

Y1 - 2010/5/25

N2 - BACKGROUND-: The term peripartum cardiomyopathy (PPCM) describes dilated cardiomyopathy (DCM) without known cause that occurs during the last month of pregnancy to 5 months postpartum. A related term, pregnancy-associated cardiomyopathy (PACM), refers to DCM onset earlier in pregnancy. Multiple studies have focused on inflammatory, immunologic, and environmental causes. An alternative hypothesis is that PPCM and PACM result, in part, from a genetic cause. In this study, we sought to test the hypothesis that rare DCM-associated mutations underlie a proportion of PACM or PPCM cases. METHODS AND RESULTS-: A systematic search of our DCM database designed for family-based genetic studies was undertaken for cases associated with pregnancy and the postpartum period; in the identified cases, clinical and molecular genetic data, including exonic and near intron/exon boundaries of DCM genes, were analyzed. Of 4110 women from 520 pedigrees in the Familial Dilated Cardiomyopathy Research Project database, we identified 45 cases of PPCM/PACM. Evidence of familial clustering with DCM was present in 23 unrelated cases. Of the 45 cases, 19 had been resequenced for known DCM genes, and 6 carried mutations. Five had PPCM, of which 3 were familial with mutations found in MYH7, SCN5A, and PSEN2, and 2 were sporadic with mutations in MYH6 and TNNT2. One case had PACM and carried a mutation in MYBPC3. CONCLUSIONS-: These findings suggest that a proportion of PPCM/PACM cases results from a genetic cause.

AB - BACKGROUND-: The term peripartum cardiomyopathy (PPCM) describes dilated cardiomyopathy (DCM) without known cause that occurs during the last month of pregnancy to 5 months postpartum. A related term, pregnancy-associated cardiomyopathy (PACM), refers to DCM onset earlier in pregnancy. Multiple studies have focused on inflammatory, immunologic, and environmental causes. An alternative hypothesis is that PPCM and PACM result, in part, from a genetic cause. In this study, we sought to test the hypothesis that rare DCM-associated mutations underlie a proportion of PACM or PPCM cases. METHODS AND RESULTS-: A systematic search of our DCM database designed for family-based genetic studies was undertaken for cases associated with pregnancy and the postpartum period; in the identified cases, clinical and molecular genetic data, including exonic and near intron/exon boundaries of DCM genes, were analyzed. Of 4110 women from 520 pedigrees in the Familial Dilated Cardiomyopathy Research Project database, we identified 45 cases of PPCM/PACM. Evidence of familial clustering with DCM was present in 23 unrelated cases. Of the 45 cases, 19 had been resequenced for known DCM genes, and 6 carried mutations. Five had PPCM, of which 3 were familial with mutations found in MYH7, SCN5A, and PSEN2, and 2 were sporadic with mutations in MYH6 and TNNT2. One case had PACM and carried a mutation in MYBPC3. CONCLUSIONS-: These findings suggest that a proportion of PPCM/PACM cases results from a genetic cause.

KW - Cardiomyopathy

KW - Genetics

KW - Pregnancy complications

UR - http://www.scopus.com/inward/record.url?scp=77953024460&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953024460&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.109.931220

DO - 10.1161/CIRCULATIONAHA.109.931220

M3 - Article

C2 - 20458009

AN - SCOPUS:77953024460

VL - 121

SP - 2176

EP - 2182

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 20

ER -